Neuronal oxidative stress is increased during one‐day ETB receptor activation in conscious rats

Infusion of the endothelin ETB receptor (ETBR) agonist sarafotoxin 6c (S6c) into rats causes a significant increase in mean arterial pressure (MAP). Increased oxidative stress is found in hypertension (HTN). Since endothelin can cause oxidative stress in vascular cells & sympathetic neurons, we hypothesized that superoxide (O2−) levels in inferior mesenteric ganglion (IMG) & blood vessels are increased in S6c‐induced HTN. All rats were instrumented with arterial and venous catheters. Treated (T) rats (n=7) received saline (iv) for 2 days, then S6c (5 pmol/kg/min) for 1 day. SHAM (S) (n=7) received saline for 3 days. MAP was recorded at the end of day 3. Vascular O2− levels were evaluated by lucigenin‐enhanced chemiluminescence & dihydroethidium (DHE)‐fluorescence. O2− levels in IMG were measured by DHE. MAP was increased markedly in T (125 ± 4 mmHg) compared to that of S (100 ± 2 mmHg). O2− levels in IMG of T rats were significantly higher than those in S (1.97:1, relative fluorescence). Both DHE and lucigenin demonstrated similar vascular O2− levels in T & S (DHE: 1.24 in arteries, 1.16 in veins; Lucigenin: 0.061 ± 0.007 nmol/min/mg tissue (T) vs 0.043 ± 0.004 (S) in arteries, 0.148 ± 0.021 vs 0.141 ± 0.017 in veins). In summary, neuronal oxidative stress is enhanced, while vascular oxidative stress is not, during the early phase of S6c infusion. This suggests a role for sympathetic nerves in S6c‐induced HTN. (NIH P01HL70687)